What can we Learn from Comparing Genetic from Non Genetic Hyperlipidemia?

Background: Extreme hypercholesterolemia may be caused by either monogenic disease, such as mutations in the receptor for LDLc, of may be multifactorial and polygenic. The purpose of the current study to compare the charectaristics of polygenic and monogenic hypercholesterolemia.

Methods: Families suspected of having familial hypercholesterolemia were collected through the MEDPED (Make Early Diagnosis Prevent Early Death) FH program. Molecular analysis of the LDLR, PCSK9 and APOB genes were done using High Resolution Melt and direct sequencing in 67 index cases. An LDL-C SNP gene score calculation for polygenic hypercholesterolaemia was done on mutation negative and positive cases. Biochemical and demographic characteristics were compared between mutation positive and mutation negative cases.

Results: Overall, 57 patients were available, 21 were mutation positive (most in the LDL receptor) and 36 were negative. Age did no differ between the two groups. Total cholesterol and LDLc levels were significantly higher in mutation positive compared with mutation negative (8.98 ± 1.92 Vs. 7.83 ± 1.77, P=0.022for total cholesteol, and 6.78 ± 1.79 Vs. 5.69 ± 1.75 P=0.026 for LDLc, respectively). Triglyceride and HDLc were not different between the groups. We than compared the LDLc SNP score, describes as a measure for polygenic hyperlipidemia, between the two groups. A higher LDL-C SNP score was found in mutation-negative cases compared with a mutation-positive patients

Conclusion: Our results demonstrate that on average, mutation positive monogenic hypecholesterolemia has a higher LDLc compared with mutation negative, Mutation negative patients, on the other hand, have a higher SNPs gene score. These results may help better understand characteristics of monogenic and polygenic hypercholesterolemia.